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Abstract Dendritic cell (DC) vaccine was among the first FDA-approved cancer immunotherapies, but has been limited by the modest cytotoxic T lymphocyte (CTL) response and therapeutic efficacy. Here we report a facile metabolic labeling approach that enables targeted modulation of adoptively transferred DCs for developing enhanced DC vaccines. We show that metabolic glycan labeling can reduce the membrane mobility of DCs, which activates DCs and improves the antigen presentation and subsequent T cell priming property of DCs. Metabolic glycan labeling itself can enhance the antitumor efficacy of DC vaccines. In addition, the cell-surface chemical tags (e.g., azido groups) introduced via metabolic glycan labeling also enable in vivo conjugation of cytokines onto adoptively transferred DCs, which further enhances CTL response and antitumor efficacy. Our DC labeling and targeting technology provides a strategy to improve the therapeutic efficacy of DC vaccines, with minimal interference upon the clinical manufacturing process.
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Cytokine-overexpressing dendritic cells for cancer immunotherapy
Abstract Dendritic cells (DCs), the main type of antigen-presenting cells in the body, act as key mediators of adaptive immunity by sampling antigens from diseased cells for the subsequent priming of antigen-specific T and B cells. While DCs can secrete a diverse array of cytokines that profoundly shape the immune milieu, exogenous cytokines are often needed to maintain the survival, proliferation, and differentiation of DCs, T cells, and B cells. However, conventional cytokine therapies for cancer treatment are limited by their low therapeutic benefit and severe side effects. The overexpression of cytokines in DCs, followed by paracrine release or membrane display, has emerged as a viable approach for controlling the exposure of cytokines to interacting DCs and T/B cells. This approach can potentially reduce the necessary dose of cytokines and associated side effects to achieve comparable or enhanced antitumor efficacy. Various strategies have been developed to enable the overexpression or chemical conjugation of cytokines on DCs for the subsequent modulation of DC–T/B-cell interactions. This review provides a brief overview of strategies that enable the overexpression of cytokines in or on DCs via genetic engineering or chemical modification methods and discusses the promise of cytokine-overexpressing DCs for the development of new-generation cancer immunotherapy.
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- Award ID(s):
- 2143673
- PAR ID:
- 10557939
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Experimental & Molecular Medicine
- Volume:
- 56
- Issue:
- 12
- ISSN:
- 2092-6413
- Format(s):
- Medium: X Size: p. 2559-2568
- Size(s):
- p. 2559-2568
- Sponsoring Org:
- National Science Foundation
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